62 research outputs found
New dipeptides containing thiazolidine-4-carboxylic acid derivatives: Synthesis and characterization using NMR techniques and X-ray data
New dipeptides, structural analogues of known immunomodulating agents, were prepared by stereospecific condensation between 2-substituted thiazolidine-4-carboxylate esters with N-substituted L-proline or L- thiaproline. The structure of these compounds has been elucidated by combination of NMR methods and X-ray analysis. In addition, NMR measurements on dipeptides indicated the presence of S-cis and S-trans conformers around the amide bonds
Exploring the Potential of Sulfonamide-Dihydropyridine Hybrids as Multitargeted Ligands for Alzheimer’s Disease Treatment
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease that has a heavy social and economic impact on all societies and for which there is still no cure. Multitarget-directed ligands (MTDLs) seem to be a promising therapeutic strategy for finding an effective treatment for this disease. For this purpose, new MTDLs were designed and synthesized in three steps by simple and cost-efficient procedures targeting calcium channel blockade, cholinesterase inhibition, and antioxidant activity. The biological and physicochemical results collected in this study allowed us the identification two sulfonamide-dihydropyridine hybrids showing simultaneous cholinesterase inhibition, calcium channel blockade, antioxidant capacity and Nrf2-ARE activating effect, that deserve to be further investigated for AD therapy.This work was supported by the Regional Council of Franche-Comté (2022Y-13659 and 13660 Accurate Project).Peer reviewe
Acetylcholinesterase Inhibition of Diversely Functionalized Quinolinones for Alzheimer's Disease Therapy
In this communication, wereport the synthesis and cholinesterase (ChE)/monoamine oxidase
(MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed
as potential multitarget small molecules (MSM) for AlzheimerÂżs disease therapy. Contrary to our
expectations, none of them showed significant human recombinant MAO inhibition, but compounds
QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and
butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent
and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 M), with Ki value in nanomolar
range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an
interesting hit for further investigation.R.A., M.S., P.B., and K.M. were supported by European Regional Development Fund/European Social Fund (ERDF/ESF, project PharmaBrain, no. CZ.02.1.01/0.0/0.0/16_025/0007444), University of Hradec Kralove
(no. SV2113-2019, VT2019-2021), and EU COST action CA15135 MuTaLig. J.M.C. thanks Ministerio de EconomĂa (MINECO, SAF2015-65586-R) and Universidad Camilo JosĂ© Cela (UCJC, grants UCJC 2020-03, and UCJC 2020-33) for support
Synthèse et évaluation de nouveaux dérivés quinoléiques impliqués dans les maladies neurodégénératives
BESANCON-BU MĂ©decine pharmacie (250562102) / SudocSudocFranceF
Maladie d'Alzheimer et vie de famille
BESANCON-BU MĂ©decine pharmacie (250562102) / SudocSudocFranceF
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